Mechanism of the onset and/or development of hereditary ataxia ; Analysis by ataxic mutant mice

遗传性共济失调的发病和/或发展机制；

基本信息

批准号：
13671139
负责人：
FUKUI Yoshihiro
金额：
$ 2.24万
依托单位：
The University OF Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671139/
关键词：
rolling mouse Nagoya Ca^<2+> channel ataxia cerebellum inferior olive 6 CRF climbing fiber mossy fiber 苔状線維前庭小脳 unipolar brush cells 蛍光免疫二重染色共焦点レーザー顕微鏡脳幹 in situ hybridization チロシン水酸化酵素ミュータントマウス

项目摘要

Rolling mouse Nagoya (RMN) is an ataxic mutant that carries a mutation in a gene encoding for P/Q-type Ca^<2+> channel α_<1A> subunit. In humans, defects in this gene are responsible for Ca^<2+> channelopathy such as familial hemiplegic migraine and episodic ataxia type-2. Corticotropin-releasing factor (CRF) is widely localized throughout the central nervous system. In the cerebellum, CRF has been found in subsets of climbing and mossy fibers, and plays a role in increasing sensitivity of cerebellar cortical neurons to glutamate, This study aimed to clarify the involvement of CRF-positive cerebellar afferent fibers in the development of ataxic symptoms of RMNIn RMN, CRF immunostaining in some climbing and mossy fibers was much more intense, but the distribution of these fibers remained the same as in non-ataxic littermates (control mice). Double immunostaining for CRF and tyrosine hydroxylase (TH) revealed that TH immunostaining abnormally appeared in some Purkinje cells receiving CRF … More -positive climbing fibers. By semi-quantitative in situ hybridization, the level of CRF mRNA signals increased in some original neurons of the climbing fibers of RMN. Signal levels in the β-nucleus and ventrolateral protrusion of inferior olive (ION) were about two-fold higher in RMN than in the controls. Signal levels in the dorsal nucleus, principal nucleus and subnucleus A of the ION were slightly but significantly higher in RMN than in the controls. In the vestibulocerebellum, the number of CRF-positive mossy fibers was much more in RMN than in the controls. Double immunofluorecence for CRF and calretinin in revealed that some CRF-positive mossy fibers closely opposed to calretinin-positive unipolar brush cells, which play roles in amplifying excitatory inputs from vestibulocerebellar mossy fibersThese results suggest that increased level of CRF in the particular subsets of climbing and mossy fibers alters excitability of cerebellar cortical neurons, involved in the ataxic symptoms of RMN Less

滚动的小鼠名古屋（RMN）是一种携带针对P/Q-Type Ca^<2+>亚基的基因，该基因中的TS是CA^<2+> ca^<2+> cotornopropin-relealeasing rigins（CRF）在小脑中，CRF在攀岩纤维的攀岩子集中发现了广泛的中枢神经系统。，在苔藓纤维和苔藓纤维中的crf静态化是更激烈的。通过半定量的原位杂交攀爬纤维。对照。在rmn中，离子的核，主核和下黄油略高于前庭中的trol for Calretinin in Reveled That Some CRFERS CLRETIN-POSITIVE iPolar Brush Cells, Which Play Role Inputtory Inputs from Vestibulocer Mossy FiberSTHESTHESE SUGGESTST THAT INCREASD EVEL OF CRF in The Particular Subsets of Climbing and Mossy Fibers Alters Excitability of Cerebellar Cortical Neurons, Involved in The Ataxic Symptoms RMN的少量